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Abstract: FR-OR37

A Prospective Study of Urinary Complement Proteins in Early Diabetic Kidney Disease in Type 1 Diabetes

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Md Dom, Zaipul I, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Moon, Salina, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Pickett, Sara D., Joslin Diabetes Center, Boston, Massachusetts, United States
  • Galecki, Andrzej, University of Michigan, Ann Arbor, Michigan, United States
  • Mauer, Michael, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Doria, Alessandro, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Niewczas, Monika A., Joslin Diabetes Center, Boston, Massachusetts, United States
Background

We identified robust urinary Complement-enriched proteomics profiles that were associated with 10-year ESKD risk in a prospective Joslin Kidney Study cohort with overt diabetic kidney disease (DKD). The role of the Complement pathway in early stages of the disease process remains unknown. This study evaluated the associations of Complement proteins and early DKD in T1D.

Methods

This prospective study included 207 participants followed for 3 years from the Preventing Early Renal Function Loss (PERL) study with T1D and baseline albuminuria (AER ≥ 20 µg/min) and CKD stages 1-3 (median AER: 127 µg/min; mean eGFR: 74 ml/min/1.73m2). Two dozen Complement proteins were measured in baseline spot urines using low-multiplex immunoassays. The kidney outcomes of interest included binary eGFR decline ≥ 3 (43% of subjects) or 5 (23%) ml/min/1.73m2/year, and a continuous eGFR slope. Model accuracy was evaluated with biostatistical and machine learning approaches.

Results

In the univariable logistic models, more than a dozen Complement proteins were associated with eGFR decline. Odds of developing eGFR decline per one tertile increase in the distribution of CFP the top Complement protein was: OR (95%CI): 2.5 (1.8, 3.6); p<10-6. The proteins represented all major components of the Complement pathway. Most of the proteins remained significant after adjustment for select clinical covariates. Albuminuria substantially impacted the Complement associations (changes in beta estimates: from 23-40%). The effect size in the principal component (PCA)-based model was larger in comparison with other models using individual proteins (Fig.1).

Conclusion

Our study of subjects with T1D and mild to moderate DKD demonstrated that Complement proteins are associated with kidney function decline over a 3-year period. These new findings suggest that the Complement pathway may play a role at earlier stages of disease process than previously assumed.

Funding

  • Other NIH Support